1. Field of Technology
The present invention relates to fusion polypeptides comprising (a) a binding site for a cytoskeleton component and (b1) an effector protein or the catalytic domain thereof or (b2) a binding site for said effector protein, and nucleic acid sequences encoding said fusion polypeptides. Furthermore, the present invention relates to various therapeutic uses of said fusion polypeptides, e.g., the treatment of diseases associated with the presence of an aberrant cell population, preferably cancer or AIDS.
2. Discussion of Related Art
For many reasons it is desirable to generate and use toxins that preferentially kill neoplastically transformed cells. In the past, this has been achieved with chemical compounds (cytotoxins, cytostatica), which with more or less specificity enabled a successful cancer treatment after surgery. Besides selectivity, a main problem of such compounds consists in the side effects but also in the lack of proficient targeting of the substance, which leads to the requirement for relatively high doses. One way to circumvent this problem is thought to be brought about by the use of targeted genetics using recombinant viruses to bring genetic elements into the tumors leading to an onsite expression of the toxin. Autonomous parvoviruses such as KRV, MVM or H-1 have been shown to preferentially propagate in and to kill neoplastically transformed cells. In addition, they consist of a class of viruses that, despite causing viremia in their infected host, mostly produce an apathogenic infection. For these reasons, autonomous parvoviruses are thought to be excellent tools for cancer gene therapy. Particular interests are focused on recombinant vectors maintaining their natural oncotropism, as well as their oncolytic and oncosuppressive potential. However, so far, little is known about the nature of the oncosuppressive potential of parvoviruses (which is independent of the parvoviral replicon) and, accordingly, the therapeutic use of said viruses, e.g., incorporated in heterologous systems such as recombinant adenoviruses or Measles viruses, for targeted gene therapy, e.g. cancer therapy is still in its infancy.